Abstract
Barrier dysfunction is the hallmark of severe lung injury, including acute respiratory distress syndrome. Efficient medical countermeasures to counteract endothelial hyperpermeability do not exist, hence the mortality rates of disorders related to barrier abnormalities are unacceptable high. The unfolded protein response is a highly conserved mechanism, which aims to support the cells against endoplasmic reticulum stress, and ATF6 is a protein sensor that triggers its activation. In the current study, we investigate the effects of ATF6 suppression in LPS-induced endothelial inflammation. Our observations suggest that Ceapin-A7, which is an ATF6 suppressor, potentiates LPS-induced STAT3 and JAK2 activation. Hence ATF6 activation may serve as a new therapeutic possibility toward diseases related to barrier dysfunction.